title: Tolerability and efficacy of pegylated interferon-α-2a in combination with imatinib for patients with chronic-phase chronic myeloid leukemia.
abstract: BACKGROUND
  The pegylated form of interferon-α-2a (PegIFNa2a) in combination with imatinib has demonstrated a molecular improvement in patients with chronic-phase chronic myeloid leukemia. However, to the authors' knowledge, the appropriate dose of PegIFNa2a has not been established to date.
  
  
  METHODS
  In the French SPIRIT trial, the authors compared 2 initial doses of PegIFNa2a, taking into account an amendment that recommended reducing that dose from 90 μg/week to 45 μg/week because of toxicities. Accordingly, 2 subgroups of patients were identified: the PegIFN90 group (171 patients who were treated with the 90-μg/week dose) and the PegIFN45 group (50 patients who were treated with the 45-μg/week dose). Both groups were compared for toxicity and efficacy.
  
  
  RESULTS
  PegIFNa2a at a dose of 90 μg/week resulted in a rate of 54% of grade 3 to 4 hematologic toxicity compared with 27% with the dose of 45 μg/week (P < .001), leading to discontinuation rates of 40% and 10%, respectively, before 6 months. The dose reduction did not significantly affect the efficacy of the combination. By 12 months, the cumulative molecular response rates (ie, BCR-ABL/abl ≤ 0.01 [IS: molecular responses graded as molecular response 4 (MR4)]) were 14% and 25%, respectively, for the subgroup treated with imatinib at a dose of 400 mg and the PegIFN90 subgroup. After the amendment, the MR4 rates were 10% and 28%, respectively, for the subgroup treated with imatinib at the 400-mg dose and PegIFN45 subgroup (P < .0001).
  
  
  CONCLUSIONS
  The results of the current study demonstrate that in combination with imatinib, the efficient dose of PegIFNa2a appears to be 45 μg/week. Society.
authors.affiliation: Department of Hematology, Cote de Nacre University Medical Center, Caen, France.
authors.forename: Hyacinthe
authors.initials: H
authors.lastname: Johnson-Ansah
authors.forename: Joelle
authors.initials: J
authors.lastname: Guilhot
authors.forename: Philippe
authors.initials: P
authors.lastname: Rousselot
authors.forename: Delphine
authors.initials: D
authors.lastname: Rea
authors.forename: Laurence
authors.initials: L
authors.lastname: Legros
authors.forename: Françoise
authors.initials: F
authors.lastname: Rigal-Huguet
authors.forename: Franck Emmanuel
authors.initials: FE
authors.lastname: Nicolini
authors.forename: François-Xavier
authors.initials: FX
authors.lastname: Mahon
authors.forename: Claude
authors.initials: C
authors.lastname: Preudhomme
authors.forename: François
authors.initials: F
authors.lastname: Guilhot
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D001549:Benzamides / Q000008:administration & dosage / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D006801:Humans; D000068877:Imatinib Mesylate; D016898:Interferon-alpha / Q000008:administration & dosage / Q000009:adverse effects; D015466:Leukemia, Myeloid, Chronic-Phase / Q000188:drug therapy*; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000009:adverse effects; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D011446:Prospective Studies; D011743:Pyrimidines / Q000008:administration & dosage / Q000009:adverse effects; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: D001549:Benzamides; D016898:Interferon-alpha; D010879:Piperazines; D011743:Pyrimidines; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000068877:Imatinib Mesylate; C100416:peginterferon alfa-2a
keywords: chronic myeloid leukemia; clinical trial; imatinib; interferon; molecular response